Document Detail

Investigation of cross-resistance to a range of photosensitizers, hyperthermia and UV light in two radiation-induced fibrosarcoma cell strains resistant to photodynamic therapy in vitro.
MedLine Citation:
PMID:  11202364     Owner:  NLM     Status:  MEDLINE    
Two distinct photodynamic therapy-resistant variants of the murine radiation-induced fibrosarcoma (RIF) cell line have been isolated. One strain displayed relative resistance over the parental RIF-1 strain to treatment with the porphyrin-based compound, polyhaematoporphyrin (PHP), whereas the other strain displayed relative resistance over the RIF-1 strain to treatment using the cationic zinc (II) pyridinium-substituted phthalocyanine (PPC). The PHP-resistant strain did not display cross-resistance to PPC-mediated treatment, and vice versa. In both PDT-resistant strains, the increased resistance could not be attributed to altered cellular growth rate, antioxidant capacity or intracellular sensitizer localization. The PHP-resistant strain displayed resistance to treatment with both short (1 h) and extended (16 h) sensitizer incubation periods, which may indicate that in this strain, the resistance has arisen through an alteration in a membrane component. Conversely, the PPC-resistant strain only displayed increased resistance over the parental cells to treatment involving the short drug incubation, which is likely to reflect the existence of a threshold effect caused by the alteration of an individual cellular target. Each resistant strain has been compared to the parental strain in terms of cellular sensitivity to treatment with a range of other photosensitizers, hyperthermia, UV light and the anticancer agent cis-diamminedichloroplatinum. The PHP-resistant strain exhibited crossresistance to photosensitization treatment using exogenously added protoporphyrin IX, and also to treatment with the anionic phthalocyanine sensitizers, zinc (II) tetrasulfonated phthalocyanine and zinc (II) tetraglycine-substituted phthalocyanine. The PPC-resistant strain did not display cross-resistance to any of the treatment strategies employed in this investigation. The results of this investigation indicate that there are at least two distinct mechanisms of PDT resistance in RIF cells, and that the mechanism of PHP resistance may, to some extent depend, upon the physical nature of the sensitizer molecule.
S Mayhew; D I Vernon; J Schofield; J Griffiths; S B Brown
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Photochemistry and photobiology     Volume:  73     ISSN:  0031-8655     ISO Abbreviation:  Photochem. Photobiol.     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-02-01     Completed Date:  2001-03-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376425     Medline TA:  Photochem Photobiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  39-46     Citation Subset:  IM    
Center for Photobiology and Photodynamic Therapy, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
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MeSH Terms
Cell Survival / drug effects,  radiation effects
Fibrosarcoma / drug therapy*,  therapy
Hyperthermia, Induced
Neoplasms, Radiation-Induced / drug therapy*,  therapy
Photosensitizing Agents / pharmacology
Radiation Tolerance
Tumor Cells, Cultured
Ultraviolet Rays
Reg. No./Substance:
0/Photosensitizing Agents

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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